In the course of previous studies of the complement component, Clq, a naturally occurring inactivator was discovered, which is the subject of the present investigation. The inactivator has been identified as a chondroitin 4-sulfate proteoglycan and has been extensively purified for purposes of more detailed characterization. Specifically, the overall size of the proteoglycan will be determined as well as the sizes of its polysaccharide and protein components; the stoichiometry of interaction between Clq and the inactivator will be examined; and the concentration of the proteoglycan in serum of normal individuals and patients with various diseases with connective tissue involvement will be determined. As part of this project, the origin of the inactivator will be investigated, particularly the possibility that it is derived from platelets or leukocytes. In view of its effect on Clq, the proteoglycan may be expected to modulate Clq activity in vivo, and attempts will be made to ascertain whether it has a role in the normal physiology of the organism as well as in certain disease states.